酵母全细胞不对称还原法合成光学纯α-羟基酸及其脱氢酶特性的研究
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摘要
生物催化以其高效的立体、位置和化学选择性成为合成光学纯手性化合物的重要手段。光学纯α-羟基酸类手性砌块是重要的精细化工中间体和手性药物前体。(R)-扁桃酸结构单元是其中最具有应用价值的代表,它不仅是半合成青霉素、头孢菌素、减肥药物和抗肿瘤药物等多种手性药物的重要砌块,还是应用广泛的手性拆分剂。微生物不对称还原途径以其理论产率高、操作简便成为合成此类化合物最直接和可行的方法。但目前仍存在催化剂稳定性差、全细胞传质阻力和终产物浓度低等问题。本论文以(R)-扁桃酸为模型产物,以克服生物催化反应中的主要限制因素、提高生物催化效率为目标,通过生物催化剂筛选、合理设计生物催化过程、对底物进行修饰和采取原位分离策略等方法使微生物不对称还原潜手性化合物合成(R)-扁桃酸类结构单元的效率明显提高。此外,对全细胞催化剂内起关键作用的醇脱氢酶进行了纯化和酶学性质研究,为其应用和进一步改造提供指导。主要结果如下:
(1)以苯甲酰甲酸为模型α-酮酸底物,针对底物极性和酸性导致的生物催化剂稳定性差的问题,采取逐步提高底物浓度的连续分批选择方法获得了具有较好操作稳定性的全细胞催化剂葡萄酒酵母(Saccharomyces ellipsoideus GIM 2.105)。该催化剂在连续分批转化20批后仍具有较高的催化活性,4℃储存5周对催化剂的活性影响很小。对此催化剂的底物特异性进行了研究,发现它对4种苯甲酰甲酸的苯环取代衍生物也具有很好的催化效果,产物(R)-扁桃酸衍生物的转化率和对映体过量值(ee值)分别保持在90%和95%以上。
(2)利用硫酸铵盐析、苯基疏水层析和凝胶过滤等纯化了S. ellipsoideus胞内D-扁桃酸脱氢酶,纯化倍数为46倍。该酶的亚基分子量为44 kDa,催化还原反应的最佳辅酶是NADPH,这些性质与其他来源的D-扁桃酸脱氢酶不同。S. ellipsoideus D-扁桃酸脱氢酶催化还原反应的最适pH和温度分别为pH 5.5和30℃,在pH 5.5– pH 8.0和温度低于30℃时保持相对稳定。
(3)研究了影响S. ellipsoideus全细胞不对称还原苯甲酰甲酸的主要因素,确定最适反应条件为:限氧条件下、pH 7.5、温度35℃、葡萄糖作为辅助底物、其最适浓度是10 g/L。在此条件下,当底物浓度为30 mmol/L时,转化48 h后,产物(R)-扁桃酸的转化率和ee值分别达到90%和99%以上。在监测S. ellipsoideus不对称还原苯甲酰甲酸的进程时发现转化初期12 h无产物生成,即存在转化初期停滞现象。通过研究关键醇脱氢酶活性、辅助底物和全细胞催化剂的传质阻力等影响因素,确定全细胞对底物/产物的传质阻力是导致此反应时间长的原因。通过改变底物结构,即将原α-酮酸底物变为α-酮酯底物,可以使不对称还原反应的时间明显降低。
(4)通过筛选更适合催化α-酮酯底物不对称还原的生物催化剂以及合理设计反应过程进一步提高了此类化合物的生物合成效率。以苯甲酰甲酸甲酯为模型α-酮酯底物,通过对反应特异性限制因素(如底物和产物的化学稳定性等)的研究,发现底物和产物的水解是此反应的主要限制因素。通过初步选择生物催化体系的pH值将底物和产物的水解损失降至最低。在此较适pH值下,对实验室保藏的37株酵母菌进行筛选,获得了对底物苯甲酰甲酸甲酯具有较高催化活性和立体选择性的全细胞催化剂酿酒酵母(Saccharomyces cerevisiae AS2.1392)。研究了其催化不对称还原α-酮酯的主要影响因素,确定最适转化条件为:pH 6.5、温度25℃、葡萄糖作为辅助底物、其最适浓度是20 g/L。在此条件下,当底物浓度为30 mmol/L时,反应在1.5 h之内结束,产物(R)-扁桃酸甲酯的产率和ee值分别达到92.4%和95%。
(5)研究了底物和产物浓度对S. cerevisiae全细胞不对称还原α-酮酯的影响,建立了底物和产物抑制模型。当底物浓度为43 mmol/L时反应初速度最大,随着底物浓度的升高或降低反应初速度降低;产物浓度的增加使反应初速度呈下降趋势,当产物浓度高于100 mmol/L时,反应初速度迅速下降。为了降低底物/产物对不对称还原反应的抑制效应,采取了树脂辅助原位分离的策略。通过测定不同类型吸附树脂对底物和产物的吸附容量和对不对称还原反应的影响,筛选出对此不对称还原反应具有较好促进作用的大孔吸附树脂NKA-Ⅱ;在适合的树脂加入量和加入模式下,产物(R)-扁桃酸甲酯的浓度可以达到128.2 mmol/L。
Biocatalysis has been an important route for the asymmetric synthesis of chiral compounds due to its remarkable enantio-, regio- and chemoselectivity. Optically active alpha-hydroxy acids are key intermediates of pharmaceuticals and fine chemicals. (R)-Mandelic acids are the most important representatives from the commercial point of view, which are not only the essential building blocks for drugs such as semi-synthetic penicillins, cephalosporins, antitumor and antiobesity agents but also the versatile resolving agents in chiral resolution processes. Special attention has been paid for the production of these compounds. Biocatalytic asymmetric reduction is an attractive alternative because of the high theoretical yield and the convenient operation conditions. However, weaknesses frequently met are the poor stability of biocatalysts, permeability issues of the whole cells and the low product concentration. In this study, (R)-mandelic acid was chosen as the model of alpha-hydroxy acids. The screening of new biocatalysts with desired properties, the systematically study of the process factors affecting the asymmetric reduction, the modification of the substrate, the application of in situ product removal technique and the purification of the key dehydrogenase were studied herein. The main results were shown as follows:
(1) Benzoylformic acid was chosen as the model of alpha-keto acid. By gradually increased substrate concentration in successive batch mode, Saccharomyces ellipsoideus GIM 2.105 was selected as an effective biocatalyst with remarkable operational stability. After twenty cycles of reuse or storage for five weeks at 4 oC, whole-cells of S. ellipsoideus maintained their activity and no obvious decrease in conversion as well as the enantiomeric excess (ee) were observed. In addition, four substituted aromatic (R)-alpha-hydroxy acids were prepared in high ee (95– >99%) and good conversion (>90%).
(2) The D-mandelate dehydrogenase from S. ellipsoideus was purified by 46-fold to homogeneity through ammonium sulphate precipitation, Phenyl-Sepharose FF and Superdex 75 gel filtration. The subunit size was about 44 kDa estimated by SDS-PAGE and it required NADPH as a cofactor, which were different from other D-mandelate dehydrogenases. Its optimal reaction pH and temperature were pH 5.5 and 30 oC. The enzyme was stable in the pH range of pH 5.5– pH 8.0 and the temperature below 30 oC.
(3) Effect of various reaction parameters on the asymmetric reduction with S. ellipsoideus was studied. The optimal conditions were determined as follows: limited oxygen supply, pH 7.5, 35 oC and 10 g/L glucose as the cosubstrate. Under the optimal conditions, yield and ee of the product attained to above 90% and 99% after 48 h. By determining the activity of intracellular mandelate dehydrogenase, studying the effect of cosubstrate and permeability issue of the whole cells, it was determined to be the permeability issue of the cell membrane to the substrate/product leading to the long reaction time. It could be shorten sharply by the modification of the substrate.
(4) Methyl benzoylformate was chosen as the model substrate of alpha-keto ester to shorten the reaction time. It was found that the decomposition of the substrate and the product was the key reaction-specific constraints (constraints dependent on the nature of the substrate and product) that limited the efficiency of this reaction. Under the preliminary selected reaction parameters that minimize these constraints, an effective whole cell biocatalyst (S. cerevisiae AS2.1392) was obtained for the asymmetric reduction of methyl benzoylformate. Under further optimized conditions, the yield and ee of the product attained to 92.4% and 95% within 1.5 h.
(5) The inhibition effect of substrate and product on the asymmetric reduction was evaluated by determining the initial reaction rate, and adsorbent resins were applied to alleviate the substrate/product inhibition. Due to the high adsorbent capacity and the promoting effect on the reaction, resin NKA-II was selected as the adsorbent material. Under the optimum resin amount and the proper adding mode, the product concentration achieved to 128.2 mmol/L.
(1)以苯甲酰甲酸为模型α-酮酸底物,针对底物极性和酸性导致的生物催化剂稳定性差的问题,采取逐步提高底物浓度的连续分批选择方法获得了具有较好操作稳定性的全细胞催化剂葡萄酒酵母(Saccharomyces ellipsoideus GIM 2.105)。该催化剂在连续分批转化20批后仍具有较高的催化活性,4℃储存5周对催化剂的活性影响很小。对此催化剂的底物特异性进行了研究,发现它对4种苯甲酰甲酸的苯环取代衍生物也具有很好的催化效果,产物(R)-扁桃酸衍生物的转化率和对映体过量值(ee值)分别保持在90%和95%以上。
(2)利用硫酸铵盐析、苯基疏水层析和凝胶过滤等纯化了S. ellipsoideus胞内D-扁桃酸脱氢酶,纯化倍数为46倍。该酶的亚基分子量为44 kDa,催化还原反应的最佳辅酶是NADPH,这些性质与其他来源的D-扁桃酸脱氢酶不同。S. ellipsoideus D-扁桃酸脱氢酶催化还原反应的最适pH和温度分别为pH 5.5和30℃,在pH 5.5– pH 8.0和温度低于30℃时保持相对稳定。
(3)研究了影响S. ellipsoideus全细胞不对称还原苯甲酰甲酸的主要因素,确定最适反应条件为:限氧条件下、pH 7.5、温度35℃、葡萄糖作为辅助底物、其最适浓度是10 g/L。在此条件下,当底物浓度为30 mmol/L时,转化48 h后,产物(R)-扁桃酸的转化率和ee值分别达到90%和99%以上。在监测S. ellipsoideus不对称还原苯甲酰甲酸的进程时发现转化初期12 h无产物生成,即存在转化初期停滞现象。通过研究关键醇脱氢酶活性、辅助底物和全细胞催化剂的传质阻力等影响因素,确定全细胞对底物/产物的传质阻力是导致此反应时间长的原因。通过改变底物结构,即将原α-酮酸底物变为α-酮酯底物,可以使不对称还原反应的时间明显降低。
(4)通过筛选更适合催化α-酮酯底物不对称还原的生物催化剂以及合理设计反应过程进一步提高了此类化合物的生物合成效率。以苯甲酰甲酸甲酯为模型α-酮酯底物,通过对反应特异性限制因素(如底物和产物的化学稳定性等)的研究,发现底物和产物的水解是此反应的主要限制因素。通过初步选择生物催化体系的pH值将底物和产物的水解损失降至最低。在此较适pH值下,对实验室保藏的37株酵母菌进行筛选,获得了对底物苯甲酰甲酸甲酯具有较高催化活性和立体选择性的全细胞催化剂酿酒酵母(Saccharomyces cerevisiae AS2.1392)。研究了其催化不对称还原α-酮酯的主要影响因素,确定最适转化条件为:pH 6.5、温度25℃、葡萄糖作为辅助底物、其最适浓度是20 g/L。在此条件下,当底物浓度为30 mmol/L时,反应在1.5 h之内结束,产物(R)-扁桃酸甲酯的产率和ee值分别达到92.4%和95%。
(5)研究了底物和产物浓度对S. cerevisiae全细胞不对称还原α-酮酯的影响,建立了底物和产物抑制模型。当底物浓度为43 mmol/L时反应初速度最大,随着底物浓度的升高或降低反应初速度降低;产物浓度的增加使反应初速度呈下降趋势,当产物浓度高于100 mmol/L时,反应初速度迅速下降。为了降低底物/产物对不对称还原反应的抑制效应,采取了树脂辅助原位分离的策略。通过测定不同类型吸附树脂对底物和产物的吸附容量和对不对称还原反应的影响,筛选出对此不对称还原反应具有较好促进作用的大孔吸附树脂NKA-Ⅱ;在适合的树脂加入量和加入模式下,产物(R)-扁桃酸甲酯的浓度可以达到128.2 mmol/L。
Biocatalysis has been an important route for the asymmetric synthesis of chiral compounds due to its remarkable enantio-, regio- and chemoselectivity. Optically active alpha-hydroxy acids are key intermediates of pharmaceuticals and fine chemicals. (R)-Mandelic acids are the most important representatives from the commercial point of view, which are not only the essential building blocks for drugs such as semi-synthetic penicillins, cephalosporins, antitumor and antiobesity agents but also the versatile resolving agents in chiral resolution processes. Special attention has been paid for the production of these compounds. Biocatalytic asymmetric reduction is an attractive alternative because of the high theoretical yield and the convenient operation conditions. However, weaknesses frequently met are the poor stability of biocatalysts, permeability issues of the whole cells and the low product concentration. In this study, (R)-mandelic acid was chosen as the model of alpha-hydroxy acids. The screening of new biocatalysts with desired properties, the systematically study of the process factors affecting the asymmetric reduction, the modification of the substrate, the application of in situ product removal technique and the purification of the key dehydrogenase were studied herein. The main results were shown as follows:
(1) Benzoylformic acid was chosen as the model of alpha-keto acid. By gradually increased substrate concentration in successive batch mode, Saccharomyces ellipsoideus GIM 2.105 was selected as an effective biocatalyst with remarkable operational stability. After twenty cycles of reuse or storage for five weeks at 4 oC, whole-cells of S. ellipsoideus maintained their activity and no obvious decrease in conversion as well as the enantiomeric excess (ee) were observed. In addition, four substituted aromatic (R)-alpha-hydroxy acids were prepared in high ee (95– >99%) and good conversion (>90%).
(2) The D-mandelate dehydrogenase from S. ellipsoideus was purified by 46-fold to homogeneity through ammonium sulphate precipitation, Phenyl-Sepharose FF and Superdex 75 gel filtration. The subunit size was about 44 kDa estimated by SDS-PAGE and it required NADPH as a cofactor, which were different from other D-mandelate dehydrogenases. Its optimal reaction pH and temperature were pH 5.5 and 30 oC. The enzyme was stable in the pH range of pH 5.5– pH 8.0 and the temperature below 30 oC.
(3) Effect of various reaction parameters on the asymmetric reduction with S. ellipsoideus was studied. The optimal conditions were determined as follows: limited oxygen supply, pH 7.5, 35 oC and 10 g/L glucose as the cosubstrate. Under the optimal conditions, yield and ee of the product attained to above 90% and 99% after 48 h. By determining the activity of intracellular mandelate dehydrogenase, studying the effect of cosubstrate and permeability issue of the whole cells, it was determined to be the permeability issue of the cell membrane to the substrate/product leading to the long reaction time. It could be shorten sharply by the modification of the substrate.
(4) Methyl benzoylformate was chosen as the model substrate of alpha-keto ester to shorten the reaction time. It was found that the decomposition of the substrate and the product was the key reaction-specific constraints (constraints dependent on the nature of the substrate and product) that limited the efficiency of this reaction. Under the preliminary selected reaction parameters that minimize these constraints, an effective whole cell biocatalyst (S. cerevisiae AS2.1392) was obtained for the asymmetric reduction of methyl benzoylformate. Under further optimized conditions, the yield and ee of the product attained to 92.4% and 95% within 1.5 h.
(5) The inhibition effect of substrate and product on the asymmetric reduction was evaluated by determining the initial reaction rate, and adsorbent resins were applied to alleviate the substrate/product inhibition. Due to the high adsorbent capacity and the promoting effect on the reaction, resin NKA-II was selected as the adsorbent material. Under the optimum resin amount and the proper adding mode, the product concentration achieved to 128.2 mmol/L.
引文
1. Nakamura K, Yamanaka R, Matsuda T, et al. Recent developments in asymmetric reduction of ketones with biocatalysts [J]. Tetrahedron: Asymmetry, 2003, 14(18):2659-2681.
2. Nakamura K, Matsuda T. Biocatalytic reduction of carbonyl groups [J]. Current Organic Chemistry, 2006, 10(11):1217-1246.
3. Matsuda T, Yamanaka R, Nakamura K. Recent progress in biocatalysis for asymmetric oxidation and reduction [J]. Tetrahedron: Asymmetry, 2009, 20(5):513-557.
4. Goldberg K, Schroer K, Lutz S, et al. Biocatalytic ketone reduction - a powerful tool for the production of chiral alcohols - part II: whole-cell reductions [J]. Applied Microbiology and Biotechnology, 2007, 76(2):249-255.
5. Kataoka M, Kita K, Wada M, et al. Novel bioreduction system for the production of chiral alcohols [J]. Applied Microbiology and Biotechnology, 2003, 62(5-6):437-445.
6.许建和,杨立荣,孙志浩,等.迅速发展中的不对称生物催化技术[J].生物加工过程, 2005, 3(3):1-6.
7. Miya H, Kawada M, Sugiyama Y. Stereoselective reduction of ethyl 2-methyl-3-oxobutanoate by bacteria [J]. Bioscience Biotechnology and Biochemistry, 1996, 60(1):95-98.
8. Groger H, Chamouleau F, Orologas N, et al. Enantioselective reduction of ketones with "Designer cells" at high substrate concentrations: Highly efficient access to functionalized optically active alcohols" [J]. Angewandte Chemie-International Edition, 2006, 45(34):5677-5681.
9. Burton S G, Cowan D A, Woodley J M. The search for the ideal biocatalyst [J]. Nature Biotechnology, 2002, 20(1):37-45.
10. Zhou B N, Gopalan A S, Vanmiddlesworth F, et al. Stereochemical control of yeast reductions. 1. Asymmetric-synthesis of L-carnitine [J]. Journal of the American Chemical Society, 1983, 105(18):5925-5926.
11. Chen C S, Zhou B N, Girdaukas G, et al. Stereochemical control of yeast reductions .2. Quantitative treatment of the kinetics of competing enzyme-systems for a single substrate [J]. Bioorganic Chemistry, 1984, 12(2):98-117.
12. Shieh W R, Gopalan A S, Sih C J. Stereochemical control of yeast reductions .5. Characterization of the oxidoreductases involved in the reduction of beta-keto-esters [J]. Journal of the American Chemical Society, 1985, 107(10):2993-2994.
13. Nakamura K, Inoue K, Ushio K, et al. Stereochemical control in microbial reduction .6. Stereochemical control on yeast reduction of alpha-keto esters - reduction by immobilized bakers-yeast in hexane [J]. Journal of Organic Chemistry, 1988, 53(11):2589-2593.
14. Ferraboschi P, Grisenti P, Manzocchi A, et al. Bakers yeast-mediated preparation of optically-active aryl alcohols and diols for the synthesis of chiral hydroxy-acids [J]. Journal of the Chemical Society-Perkin Transactions 1, 1990, (9):2469-2474.
15. Zhu D M, Rios B E, Rozzell J D, et al. Evaluation of substituent effects on activity and enantioselectivity in the enzymatic reduction of aryl ketones [J]. Tetrahedron: Asymmetry, 2005, 16(8):1541-1546.
16. Yang Y, Zhu D, Piegat T J, et al. Enzymatic ketone reduction: mapping the substrate profile of a short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae [J]. Tetrahedron: Asymmetry, 2007, 18(15):1799-1803.
17. Kurbanoglu E B, Zilbeyaz K, Kurbanoglu N I, et al. Enantioselective reduction of substituted acetophenones by Aspergillus niger [J]. Tetrahedron: Asymmetry, 2007, 18(10):1159-1162.
18. Pollard D J, Woodley J M. Biocatalysis for pharmaceutical intermediates: the future is now [J]. Trends in Biotechnology, 2007, 25(2):66-73.
19. Chen Y, Lin H, Xu X, et al. Preparation the key intermediate of angiotensin-converting enzyme (ACE) inhibitors: High enantioselective production of ethyl (R)-2-hydroxy-4-phenylbutyrate with Candida boidinii CIOC21 [J]. Advanced Synthesis & Catalysis, 2008, 350(3):426-430.
20. Hiraoka C, Matsuda M, Suzuki Y, et al. Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones [J]. Tetrahedron: Asymmetry, 2006, 17(24):3358-3367.
21. Voss C V, Gruber C C, Kroutil W. A biocatalytic one-pot oxidation/reduction sequence for the deracemisation of a sec-alcohol [J]. Tetrahedron: Asymmetry, 2007, 18(2):276-281.
22. Mateo C, Palomo J M, Fernandez-Lorente G, et al. Improvement of enzyme activity, stability and selectivity via immobilization techniques [J]. Enzyme and Microbial Technology, 2007, 40(6):1451-1463.
23. Kizaki N, Yasohara Y, Hasegawa J, et al. Synthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate by Escherichia coli transformant cells coexpressing the carbonyl reductase and glucose dehydrogenase genes [J]. Applied Microbiology and Biotechnology, 2001, 55(5):590-595.
24. Li Y N, Shi X A, Zong M H, et al. Asymmetric reduction of 2-octanone in water/organic solvent biphasic system with Baker's yeast FD-12 [J]. Enzyme and Microbial Technology, 2007, 40(5):1305-1311.
25. Tsujigami T, Sugai T, Ohta H. Microbial asymmetric reduction of alpha-hydroxyketones in the anti-Prelog selectivity [J]. Tetrahedron: Asymmetry, 2001, 12(18):2543-2549.
26. Katz M, Sarvary I, Frejd T, et al. An improved stereoselective reduction of a bicyclic diketone by Saccharomyces cerevisiae combining process optimization and strain engineering [J]. Applied Microbiology and Biotechnology, 2002, 59(6):641-648.
27. Shi Y G, Fang Y, Ren Y P, et al. Applying alpha-phenacyl chloride to the enantioselective reduction of ethyl 2-oxo-4-phenylbutyrate with baker's yeast [J]. Journal of Chemical Technology and Biotechnology, 2009, 84(5):681-688.
28. Vaijayanthi T, Chadha A. Asymmetric reduction of aryl imines using Candida parapsilosis ATCC 7330 [J]. Tetrahedron: Asymmetry, 2008, 19(1):93-96.
29.倪宏亮.面包酵母催化β-羰基酯类不对称还原的研究[D]: [博士学位论文].杭州:浙江大学, 2007.
30. Li H M, Zhu D M, Hua L, et al. Enantioselective reduction of diaryl Ketones catalyzed by a carbonyl reductase from Sporobolomyces salmonicolor and its mutant enzymes [J]. Advanced Synthesis & Catalysis, 2009, 351(4):583-588.
31. Ei-Zahab B, Donnelly D, Wang P. Particle-tethered NADH for production of methanol from CO2 catalyzed by coimmobilized enzymes [J]. Biotechnology and Bioengineering, 2008, 99(3):508-514.
32. Yang H, Jonsson A, Wehtje E, et al. The enantiomeric purity of alcohols formed by enzymatic reduction ketones can be improved by optimisation of the temperature and by using a high co-substrate concentration [J]. Biochimica Et Biophysica Acta-General Subjects, 1997, 1336(1):51-58.
33. Pham V T, Phillips R S, Ljungdahl L G. Temperature dependent enantiospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus [J]. Journal of the American Chemical Society, 1989, 111(5):1935-1936.
34. Pham V T, Phillips R S. Effects of substrate structure and temperature on the stereospecificity of secondary alcohol-dehydrogenase from Thermoanaerobacter ethanolicus [J]. Journal of the American Chemical Society, 1990, 112(9):3629-3632.
35. Woodley J M, Bisschops M, Straathof A J J, et al. Future directions for in-situ product removal (ISPR) [J]. Journal of Chemical Technology and Biotechnology, 2008, 83(2):121-123.
36. Houng J Y, Liau J S. Applying slow-release biocatalysis to the asymmetric reduction of ethyl 4-chloroacetoacetate [J]. Biotechnology Letters, 2003, 25:17-21.
37. Yang Z H, Zeng R, Chang X, et al. Toxicity of aromatic ketone to yeast cell and improvement of the asymmetric reduction of aromatic ketone catalyzed by yeast cell with the introduction of resin adsorption [J]. Food Technology and Biotechnology, 2008, 46(3):322-327.
38. Hilker I, Gutierrez M C, Furstoss R, et al. Preparative scale Baeyer-Villiger biooxidation at high concentration using recombinant Escherichia coli and in situ substrate feeding and product removal process [J]. Nature Protocols, 2008, 3(3):546-554.
39. Vicenzi J T, Zmijewski M J, Reinhard M R, et al. Large-scale stereoselective enzymatic ketone reduction with in situ product removal via polymeric adsorbent resins [J]. Enzyme and Microbial Technology, 1997, 20(7):494-499.
40. D'Arrigo P, Fantoni G P, Servi S, et al. The effect of absorbing resins On substrate concentration and enantiomeric excess in yeast reduction [J]. Tetrahedron: Asymmetry, 1997, 8(14):2375-2379.
41. Coppola G M, Schuster H F. Mandelic acid. In: Walter G, editor.α-Hydroxy acids in enantioselective syntheses. Weinheim: Wiley-VCH 2003. p. 137-165.
42.黄斌,孙兴邦.盐酸奥昔布宁的合成[J].中国医药工业杂志, 1996, 27(9):387-389.
43. Furlenmeier A, Quitt P, Vogler K, et al., inventors; 6-Acyl derivatives of aminopenicillanic acid U.S. patent 3,957,758. 1976.
44. Bichel H, Kocsis K, Peter H, inventors; Cephalosporins having anα-acyloxyacetic acid side chain. U.S. patent 4,067,979. 1978.
45. Mills J, Schmiegel K K, Shaw W N, inventors; Phenethanolamines, compositions containing the same, and method for effecting weight control. U.S. patent 4,391,826. 1983.
46. Surivet J P, Vatele J M. Total synthesis of antitumor Goniothalamus styryllactones [J]. Tetrahedron, 1999, 55(45):13011-13028.
47. Ema T, Okita N, Ide S, et al. Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E-coli: toward practical and green access to clopidogrel [J]. Organic & Biomolecular Chemistry, 2007, 5(8):1175-1176.
48.张金波,杨吉春,刘若霖,等.扁桃酸类杀菌剂的创制及其研究进展[J].农药, 2009, 48(2):82-87.
49. Whitesell J K, Reynolds D. Resolution of chiral alcohols with mandelic acid [J]. Journal of Organic Chemistry, 1983, 48(20):3548-3551.
50. Kinbara K, Sakai K, Hashimoto Y, et al. Design of resolving reagents: p-Substituted mandelic acids as resolving reagents for 1-arylalkylamines [J]. Tetrahedron: Asymmetry, 1996, 7(6):1539-1542.
51. Bauer T, Gaiewiak J. alpha-Hydroxy carboxylic acids as ligands for enantioselective addition reactions of organoaluminum reagents to aromatic and aliphatic aldehydes [J]. Tetrahedron: Asymmetry, 2005, 16(4):851-855.
52. Bauer T, Gajewiak J. alpha-Hydroxy carboxylic acids as ligands for enantioselective diethylzinc additions to aromatic and aliphatic aldehydes [J]. Tetrahedron, 2004, 60(41):9163-9170.
53. Yamazaki Y, Maeda H. Enzymatic synthesis of optically pure (R)-(-)-mandelic acid and other 2- hydroxycarboxylic acids: Screening for the enzyme, and its purification, characterization and use. [J]. Agricultural and Biological Chemistry, 1986, 50(10):2621-2631.
54. Hosono K, Kajiwara S, Yamazaki Y, et al. Construction of a bioreactor for production of (R)-(-)-mandelate, a typical specialty chemical [J]. Journal of Biotechnology, 1990, 14(2):149-156.
55. Vasicracki D, Jonas M, Wandrey C, et al. Continuous (R)-mandelic acid production in an enzyme membrane reactor [J]. Applied Microbiology and Biotechnology, 1989, 31(3):215-222.
56. Xiao M T, Huang Y Y, Shi X A, et al. Bioreduction of phenylglyoxylic acid to R-(-)-mandelic acid by Saccharomyces cerevisiae FD11b [J]. Enzyme and Microbial Technology, 2005, 37(6):589-596.
57.黄雅燕,肖美添,郭养浩.微生物转化苯乙酮酸合成R-(-)-扁桃酸[J].福州大学学报(自然科学版), 2006, 34(3):435-438.
58. Wada Y, Iwai S, Tamura Y, et al. A new family of D-2-hydroxyacid dehydrogenases that comprises D-mandelate dehydrogenases and 2-ketopantoate reductases [J]. Bioscience Biotechnology and Biochemistry, 2008, 72(4):1087-1094.
59. Hummel W, Schutte H, Kula M R. D-(-)-mandelic acid dehydrogenase from Lactobacillus curvatus [J]. Applied Microbiology and Biotechnology, 1988, 28(4-5):433-439.
60. Baker D P, Fewson C A. Purification and characterization of D-(-)-mandelate dehydrogenase from Rhodotorula graminis [J]. Journal of General Microbiology, 1989, 135:2035-2044.
61. Tamura Y, Ohkubo A, Iwai S, et al. Two forms of NAD-dependent D-mandelate dehydrogenase in Enterococcus faecalis IAM 10071 [J]. Applied and Environmental Microbiology, 2002, 68(2):947-951.
62.严芬,郭养浩,陈芬玲,等.酿酒酵母中D-(-)-扁桃酸脱氢酶性质研究[J].福州大学学报(自然科学版), 2008, 36(6):905-909.
63. Milagre H M S, Milagre C D F, Moran P J S, et al. Reduction of ethyl benzoylformate mediated by Saccharomyces cerevisiae entrapped in alginate fibers with double gel layers in a continuously operated reactor [J]. Enzyme and Microbial Technology, 2005, 37(1):121-125.
64. Kratzer R, Egger S, Nidetzky B. Integration of enzyme, strain and reaction engineering to overcome limitations of Baker's yeast in the asymmetric reduction of alpha-keto esters [J]. Biotechnology and Bioengineering, 2008, 101(5):1094-1101.
65. He C M, Chang D L, Zhang J. Asymmetric reduction of substituted alpha- and beta-ketoesters by Bacillus pumilus Phe-C3 [J]. Tetrahedron: Asymmetry, 2008, 19(11):1347-1351.
66. Kayser M M, Mihovilovic M D, Kearns J, et al. Baker's yeast-mediated reductions of alpha-keto esters and an alpha-keto-beta-lactam. Two routes to the paclitaxel side chain [J]. Journal of Organic Chemistry, 1999, 64(18):6603-6608.
67. Chen Y Z, Xu J G, Xu X Y, et al. Enantiocomplementary preparation of (S)- and (R)-mandelic acid derivatives via alpha-hydroxylation of 2-arylacetic acid derivatives and reduction of alpha-ketoester using microbial whole cells [J]. Tetrahedron: Asymmetry, 2007, 18(21):2537-2540.
68. Meyer D, Buehler B, Schmid A. Process and catalyst design objectives for specific redox biocatalysis. Advances in Applied Microbiology, Vol 59. San Diego: Elsevier Academic Press Inc; 2006. p. 53-91.
69. Li G Y, Huang K L, Jiang Y R, et al. Production of (R)-mandelic acid by immobilized cells of Saccharomyces cerevisiae on chitosan carrier [J]. Process Biochemistry, 2007, 42(10):1465-1469.
70. Xiao M T, Huang Y Y, Ye J, et al. Study on the kinetic characteristics of the asymmetric production of R-(-)-mandelic acid with immobilized Saccharomyces cerevisiae FD11b [J]. Biochemical Engineering Journal, 2008, 39(2):311-318.
71. Polizzi K M, Bommarius A S, Broering J M, et al. Stability of biocatalysts [J]. Current Opinion in Microbiology, 2007, 11(2):220-225.
72. Tishkov V I, Popov V O. Protein engineering of formate dehydrogenase [J]. Biomolecular Engineering, 2006, 23(2-3):89-110.
73. Wu J C, He Z M, Yao C Y, et al. Increased activity and stability of Candida rugosa lipase in reverse micelles formed by chemically modified AOT in isooctane [J]. Journal of Chemical Technology and Biotechnology, 2001, 76(9):949-953.
74. Fujita K, Forsyth M, MacFarlane D R, et al. Unexpected improvement in stability and utility of cytochrome c by solution in biocompatible ionic liquids [J]. Biotechnology and Bioengineering, 2006, 94(6):1209-1213.
75. Chen R R Z. Permeability issues in whole-cell bioprocesses and cellular membrane engineering [J]. Applied Microbiology and Biotechnology, 2007, 74(4):730-738.
76.于明安,朱晓冰,祁巍,等. CTAB透性化酵母细胞生物催化合成(S)-(+)-3-羟基丁酸乙酯[J].催化学报, 2005, 26(7):609-613.
77. Zhang J, Witholt B, Li Z. Coupling of permeabilized microorganisms for efficient enantioselective reduction of ketone with cofactor recycling [J]. Chemical Communications, 2006, (4):398-400.
78. Ni Y, Chen R R. Accelerating whole-cell biocatalysis by reducing outer membrane permeability barrier [J]. Biotechnology and Bioengineering, 2004, 87(6):804-811.
79. Zhang B B, Lou W Y, Zong M H, et al. Efficient synthesis of enantiopure (S)-4-(trimethylsilyl)-3-butyn-2-ol via asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one with immobilized Candida parapsilosis CCTCC M203011 cells [J]. Journal of Molecular Catalysis B-Enzymatic, 2008, 54(3-4):122-129.
80. Wang W, Zong M H, Lou W Y. Use of an ionic liquid to improve asymmetric reduction of 4 '-methoxyacetophenone catalyzed by immobilized Rhodotorula sp AS2.2241 cells [J]. Journal of Molecular Catalysis B-Enzymatic, 2009, 56(1):70-76.
81. Stark D, von Stockar U. In situ product removal (ISPR) in whole cell biotechnology during the last twenty years. In: von Stockar U, van der Wielen LAM, editors. Process integration in biochemical engineering: Springer-Verlag New York Inc.; Springer-Verlag GmbH & Co. KG; 2003. p. 149-175.
82. Coward-Kelly G, Chen R R. A Window into Biocatalysis and Biotransformations [J]. Biotechnology Progress, 2007.
83. Woodley J M. New opportunities for biocatalysis: making pharmaceutical processes greener [J]. Trends in Biotechnology, 2008, 26(6):321-327.
84. Straathof A J J, Panke S, Schmid A. The production of fine chemicals by biotransformations [J]. Current Opinion in Biotechnology, 2002, 13(6):548-556.
85. Ishige T, Honda K, Shimizu S. Whole organism biocatalysis [J]. Current Opinion in Chemical Biology, 2005, 9(2):174-180.
86. Schmid A, Dordick J S, Hauer B, et al. Industrial biocatalysis today and tomorrow [J]. Nature, 2001, 409(6817):258-268.
87.张辉.微生物全细胞转化法制备(R)-扁桃酸的研究[D]: [硕士学位论文].无锡:江南大学, 2006.
88.黄汉荣.扁桃酸氧化还原酶的筛选及应用研究[D]: [硕士学位论文].上海:华东理工大学, 2005.
89. Kesslin G, Kelly K W, inventors; Resolution of racemic mandelic acid. U.S. patent 4,322,548. 1982.
90. Schoemaker H E, Mink D, Wubbolts M G. Dispelling the myths - Biocatalysis in industrial synthesis [J]. Science, 2003, 299(5613):1694-1697.
91. Groger H. Enzymatic routes to enantiomerically pure aromatic alpha-hydroxy carboxylic acids: A further example for the diversity of biocatalysis [J]. Advanced Synthesis & Catalysis, 2001, 343(6-7):547-558.
92. Weinstock L M, Currie R B, Lovell A V. A general, one-step synthesis of alpha-keto ester [J]. Synthetic Communications, 1981, 11(12):943-946.
93. Yu M A, Hou Y, Gong G H, et al. Effects of industrial storage on the bioreduction capacity of brewer's yeast [J]. Journal of Industrial Microbiology & Biotechnology, 2009, 36(1):157-162.
94. Kaluzna I A, Rozzell J D, Kambourakis S. Ketoreductases: stereoselective catalysts for the facile synthesis of chiral alcohols [J]. Tetrahedron: Asymmetry, 2005, 16(22):3682-3689.
95. Zhu D M, Stearns J E, Ramirez M, et al. Enzymatic enantioselective reduction of alpha-ketoesters by a thermostable 7 alpha-hydroxysteroid dehydrogenase from Bacteroides fragilis [J]. Tetrahedron, 2006, 62(18):4535-4539.
96. Zhu D M, Yang Y, Buynak J D, et al. Stereoselective ketone reduction by a carbonyl reductase from Sporobolomyces salmonicolor. Substrate specificity, enantioselectivity and enzyme-substrate docking studies [J]. Organic & Biomolecular Chemistry, 2006, 4(14):2690-2695.
97. Wei Z L, Li Z Y, Lin G Q. anti-Prelog microbial reduction of aryl alpha-halomethyl or alpha-hydroxymethyl ketones with Geotrichum sp 38 [J]. Tetrahedron, 1998, 54(43):13059-13072.
98. Fronza G, Fuganti C, Grasselli P, et al. On the mode of bakers-yeast transformation of 3-chloropropiophenone and related ketones - synthesis of (2S)-[2,2H]propiophenone, (R)-fluoxetine, (R)-fenfluramine and (S)-fenfluramine [J]. Journal of Organic Chemistry, 1991, 56(21):6019-6023.
99. Kumar A, Ner D H, Dike S Y. A new chemoenzymatic enantioselective synthesis of R-(-)-tomoxetine, (R)-fluoxetine and (S)-fluoxetine [J]. Tetrahedron Letters, 1991, 32(16):1901-1904.
100. Yamazaki N, Atobe M, Kibayashi C. Nucleophilic addition of methyllithium to chiral oxime ethers: asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue [J]. Tetrahedron Letters, 2001, 42(30):5029-5032.
101. Kumar P, Upadhyay R K, Pandey R K. Asymmetric dihydroxylation route to (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine [J]. Tetrahedron-Asymmetry, 2004, 15(24):3955-3959.
102.何军邀.微生物细胞非水相催化羰基化合物的不对称还原[D]: [博士学位论文].无锡:江南大学, 2006.
103.徐小琳,徐岩,穆晓清. NAD(P)依赖型氧化还原酶分离纯化技术进展[J].工业微生物, 2005, 35(1):49-54.
104.汪家政,范明.蛋白质技术手册:科学出版社; 2000.
105. Bradford M M. Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding [J]. Analytical Biochemistry, 1976, 72(1-2):248-254.
106. Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacterio phage T-4 [J]. Nature (London), 1970, 227(5259):680-685.
107.Zheng Y C, Si X H, He Q H, et al. Yak lactate dehydrogenase A4: Purification, properties, and cDNA cloning [J]. Bioscience Biotechnology and Biochemistry, 2008, 72(9):2448-2451.
108. Eprintsev A T, Klimova M A, Shikhalieva K D, et al. Isolation and purification of malate dehydrogenase isoforms from phototrophic purple bacteria Rhodobacter sphaeroides and Rhodopseudomonas palustris [J]. Biology Bulletin, 2008, 35(6):585-591.
109.严芬,郭养浩,林木仙,等.酿酒酵母中的D-(-)-扁桃酸脱氢酶[J].药物生物技术, 2007, 14(1):43-47.
110. Engelking H, Pfaller R, Wich G, et al. Reaction engineering studies on beta-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae [J]. Enzyme and Microbial Technology, 2006, 38(3-4):536-544.
111. He J Y, Zhou L M, Wang P, et al. Microbial reduction of ethyl acetoacetate to ethyl (R)-3-hydroxybutyrate in an ionic liquid containing system [J]. Process Biochemistry, 2009, 44(3):316-321.
112. Slavik J, Kotyk A. Intracellular pH distribution and transmembrane pH profile of yeast-cells [J]. Biochimica Et Biophysica Acta, 1984, 766(3):679-684.
113. Phillips R S. Temperature modulation of the stereochemistry of enzymatic catalysis: Prospects for exploitation [J]. Trends in Biotechnology, 1996, 14(1):13-16.
114. Sih C J, Chen C S. Microbial asymmetric catalysis - enantioselective reduction of ketones [J]. Angewandte Chemie-International Edition in English, 1984, 23(8):570-578.
115. Woodley J M. Microbial biocatalytic processes and their development. Advances in Applied Microbiology, Vol 60. San Diego: Elsevier Academic Press Inc; 2006. p. 1-15.
116. Hu X P, Mamoto R, Shimomura Y, et al. Cell surface structure enhancing uptake of polyvinyl alcohol (PVA) is induced by PVA in the PVA-utilizing Sphingopyxis sp strain 113P3 [J]. Archives of Microbiology, 2007, 188(3):235-241.
117. Guo J L, Mu X Q, Zheng C G, et al. A highly stable whole-cell biocatalyst for the enantioselective synthesis of optically active alpha-hydroxy acids [J]. Journal of Chemical Technology and Biotechnology, 2009, 84(12):1787-1792.
118. Pscheidt B, Glieder A. Yeast cell factories for fine chemical and API production [J]. Microbial Cell Factories, 2008, 7:49.
119. Secundo F, Phillips R S. Effects of pH on enantiospecificity of alcohol dehydrogenases from Thermoanaerobacter ethanolicus and horse liver [J]. Enzyme and Microbial Technology, 1996, 19(7):487-492.
120. Phillips R S. Temperature effects on stereochemistry of enzymatic reactions [J]. Enzyme and Microbial Technology, 1992, 14(5):417-419.
121. Leon R, Fernandes P, Pinheiro H M, et al. Whole-cell biocatalysis in organic media [J]. Enzyme and Microbial Technology, 1998, 23(7-8):483-500.
122. Zhang B L, Pionnier S. Cofactor recycling mechanism in asymmetric biocatalytic reduction of carbonyl compounds mediated by yeast: Which is the efficient electron donor? [J]. Chemistry-a European Journal, 2003, 9(15):3604-3610.
123.高炳学,林金萍,魏东芝.酿酒酵母不对称合成(R)-(-)-扁桃酸甲酯[J].华东理工大学学报(自然科学版), 2008, 34(3):350-353.
124. Bechtold M, Panke S. In situ Product Recovery Integrated with Biotransformations [J]. Chimia, 2009, 63(6):345-348.
125. Kim P Y, Pollard D J, Woodley J M. Substrate supply for effective biocatalysis [J]. Biotechnology Progress, 2007, 23(1):74-82.
126. Han K, Levenspiel O. Extended monod kinetics for substrate, product, and cell-inhibition [J]. Biotechnology and Bioengineering, 1988, 32(4):430-437.
127. Amanullah A, Hewitt C J, Nienow A W, et al. Fed-batch bioconversion of indene to cis-indandiol [J]. Enzyme and Microbial Technology, 2002, 31(7):954-967.
128. Chin-Joe I, Straathof A J J, Pronk J T, et al. Effect of high product concentration in a dual fed-batch asymmetric 3-oxo ester reduction by baker's yeast [J]. Biocatalysis and Biotransformation, 2002, 20(5):337-345.
129. Casey J T, Walsh P K, O’Shea D G. Characterisation of adsorbent resins for the recovery of geldanamycin from fermentation broth [J]. Separation and Purification Technology, 2006.
130. Dongliang H, Cuiqing M, Lifu S, et al. Enhanced vanillin production from ferulic acid using adsorbent resin [J]. Applied Microbiology and Biotechnology, 2007, 74(4):783-790.
131. Roddick F A, Britz M L. Production of hexanoic acid by free and immobilised cells of Megasphaera elsdenii: Influence of in-situ product removal using ion exchange resin [J]. Journal of Chemical Technology and Biotechnology, 1997, 69(3):383-391.
132. van den Berg C, Wierckx N, Vente J, et al. Solvent-impregnated resins as an in situ product recovery tool for phenol recovery from Pseudomonas putida S12TPL fermentations [J]. Biotechnology and Bioengineering, 2008, 100(3):466-472.
133. Hilker I, Gutierrez M C, Alphand V, et al. Microbioloical transformations 57. Facile and efficient resin-based in situ SFPR preparative-scale synthesis of an enantiopure "unexpected" lactone regioisomer via a Baeyer-Villiger oxidation process [J]. Organic Letters, 2004, 6(12):1955-1958.
134. Ni Y, Xu Y, Yang W, et al. Promoting effect of resin adsorption on asymmetric reduction of acetophenone catalyzed by Rhodotorula sp Cells [J]. Chinese Journal of Organic Chemistry, 2008, 28(12):2137-2141.
135. Hilker I, Wohlgemuth R, Alphand V, et al. Scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity using a resin-based in situ SFPR strategy [J]. Biotechnology and Bioengineering, 2005, 92(6):702-710.
136. Hilker I, Alphand V, Wohlgemuth R, et al. Microbial transformations, 56. Preparative scale asymmetric Baeyer-Villiger oxidation using a highly productive "two-in-One" resin-based in situ SFPR concept [J]. Advanced Synthesis & Catalysis, 2004, 346(2-3):203-214.
137. Darrigo P, Fantoni G P, Servi S, et al. The effect of absorbing resins on substrate concentration and enantiomeric excess in yeast reduction [J]. Tetrahedron: Asymmetry, 1997, 8(14):2375-2379.
2. Nakamura K, Matsuda T. Biocatalytic reduction of carbonyl groups [J]. Current Organic Chemistry, 2006, 10(11):1217-1246.
3. Matsuda T, Yamanaka R, Nakamura K. Recent progress in biocatalysis for asymmetric oxidation and reduction [J]. Tetrahedron: Asymmetry, 2009, 20(5):513-557.
4. Goldberg K, Schroer K, Lutz S, et al. Biocatalytic ketone reduction - a powerful tool for the production of chiral alcohols - part II: whole-cell reductions [J]. Applied Microbiology and Biotechnology, 2007, 76(2):249-255.
5. Kataoka M, Kita K, Wada M, et al. Novel bioreduction system for the production of chiral alcohols [J]. Applied Microbiology and Biotechnology, 2003, 62(5-6):437-445.
6.许建和,杨立荣,孙志浩,等.迅速发展中的不对称生物催化技术[J].生物加工过程, 2005, 3(3):1-6.
7. Miya H, Kawada M, Sugiyama Y. Stereoselective reduction of ethyl 2-methyl-3-oxobutanoate by bacteria [J]. Bioscience Biotechnology and Biochemistry, 1996, 60(1):95-98.
8. Groger H, Chamouleau F, Orologas N, et al. Enantioselective reduction of ketones with "Designer cells" at high substrate concentrations: Highly efficient access to functionalized optically active alcohols" [J]. Angewandte Chemie-International Edition, 2006, 45(34):5677-5681.
9. Burton S G, Cowan D A, Woodley J M. The search for the ideal biocatalyst [J]. Nature Biotechnology, 2002, 20(1):37-45.
10. Zhou B N, Gopalan A S, Vanmiddlesworth F, et al. Stereochemical control of yeast reductions. 1. Asymmetric-synthesis of L-carnitine [J]. Journal of the American Chemical Society, 1983, 105(18):5925-5926.
11. Chen C S, Zhou B N, Girdaukas G, et al. Stereochemical control of yeast reductions .2. Quantitative treatment of the kinetics of competing enzyme-systems for a single substrate [J]. Bioorganic Chemistry, 1984, 12(2):98-117.
12. Shieh W R, Gopalan A S, Sih C J. Stereochemical control of yeast reductions .5. Characterization of the oxidoreductases involved in the reduction of beta-keto-esters [J]. Journal of the American Chemical Society, 1985, 107(10):2993-2994.
13. Nakamura K, Inoue K, Ushio K, et al. Stereochemical control in microbial reduction .6. Stereochemical control on yeast reduction of alpha-keto esters - reduction by immobilized bakers-yeast in hexane [J]. Journal of Organic Chemistry, 1988, 53(11):2589-2593.
14. Ferraboschi P, Grisenti P, Manzocchi A, et al. Bakers yeast-mediated preparation of optically-active aryl alcohols and diols for the synthesis of chiral hydroxy-acids [J]. Journal of the Chemical Society-Perkin Transactions 1, 1990, (9):2469-2474.
15. Zhu D M, Rios B E, Rozzell J D, et al. Evaluation of substituent effects on activity and enantioselectivity in the enzymatic reduction of aryl ketones [J]. Tetrahedron: Asymmetry, 2005, 16(8):1541-1546.
16. Yang Y, Zhu D, Piegat T J, et al. Enzymatic ketone reduction: mapping the substrate profile of a short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae [J]. Tetrahedron: Asymmetry, 2007, 18(15):1799-1803.
17. Kurbanoglu E B, Zilbeyaz K, Kurbanoglu N I, et al. Enantioselective reduction of substituted acetophenones by Aspergillus niger [J]. Tetrahedron: Asymmetry, 2007, 18(10):1159-1162.
18. Pollard D J, Woodley J M. Biocatalysis for pharmaceutical intermediates: the future is now [J]. Trends in Biotechnology, 2007, 25(2):66-73.
19. Chen Y, Lin H, Xu X, et al. Preparation the key intermediate of angiotensin-converting enzyme (ACE) inhibitors: High enantioselective production of ethyl (R)-2-hydroxy-4-phenylbutyrate with Candida boidinii CIOC21 [J]. Advanced Synthesis & Catalysis, 2008, 350(3):426-430.
20. Hiraoka C, Matsuda M, Suzuki Y, et al. Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones [J]. Tetrahedron: Asymmetry, 2006, 17(24):3358-3367.
21. Voss C V, Gruber C C, Kroutil W. A biocatalytic one-pot oxidation/reduction sequence for the deracemisation of a sec-alcohol [J]. Tetrahedron: Asymmetry, 2007, 18(2):276-281.
22. Mateo C, Palomo J M, Fernandez-Lorente G, et al. Improvement of enzyme activity, stability and selectivity via immobilization techniques [J]. Enzyme and Microbial Technology, 2007, 40(6):1451-1463.
23. Kizaki N, Yasohara Y, Hasegawa J, et al. Synthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate by Escherichia coli transformant cells coexpressing the carbonyl reductase and glucose dehydrogenase genes [J]. Applied Microbiology and Biotechnology, 2001, 55(5):590-595.
24. Li Y N, Shi X A, Zong M H, et al. Asymmetric reduction of 2-octanone in water/organic solvent biphasic system with Baker's yeast FD-12 [J]. Enzyme and Microbial Technology, 2007, 40(5):1305-1311.
25. Tsujigami T, Sugai T, Ohta H. Microbial asymmetric reduction of alpha-hydroxyketones in the anti-Prelog selectivity [J]. Tetrahedron: Asymmetry, 2001, 12(18):2543-2549.
26. Katz M, Sarvary I, Frejd T, et al. An improved stereoselective reduction of a bicyclic diketone by Saccharomyces cerevisiae combining process optimization and strain engineering [J]. Applied Microbiology and Biotechnology, 2002, 59(6):641-648.
27. Shi Y G, Fang Y, Ren Y P, et al. Applying alpha-phenacyl chloride to the enantioselective reduction of ethyl 2-oxo-4-phenylbutyrate with baker's yeast [J]. Journal of Chemical Technology and Biotechnology, 2009, 84(5):681-688.
28. Vaijayanthi T, Chadha A. Asymmetric reduction of aryl imines using Candida parapsilosis ATCC 7330 [J]. Tetrahedron: Asymmetry, 2008, 19(1):93-96.
29.倪宏亮.面包酵母催化β-羰基酯类不对称还原的研究[D]: [博士学位论文].杭州:浙江大学, 2007.
30. Li H M, Zhu D M, Hua L, et al. Enantioselective reduction of diaryl Ketones catalyzed by a carbonyl reductase from Sporobolomyces salmonicolor and its mutant enzymes [J]. Advanced Synthesis & Catalysis, 2009, 351(4):583-588.
31. Ei-Zahab B, Donnelly D, Wang P. Particle-tethered NADH for production of methanol from CO2 catalyzed by coimmobilized enzymes [J]. Biotechnology and Bioengineering, 2008, 99(3):508-514.
32. Yang H, Jonsson A, Wehtje E, et al. The enantiomeric purity of alcohols formed by enzymatic reduction ketones can be improved by optimisation of the temperature and by using a high co-substrate concentration [J]. Biochimica Et Biophysica Acta-General Subjects, 1997, 1336(1):51-58.
33. Pham V T, Phillips R S, Ljungdahl L G. Temperature dependent enantiospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus [J]. Journal of the American Chemical Society, 1989, 111(5):1935-1936.
34. Pham V T, Phillips R S. Effects of substrate structure and temperature on the stereospecificity of secondary alcohol-dehydrogenase from Thermoanaerobacter ethanolicus [J]. Journal of the American Chemical Society, 1990, 112(9):3629-3632.
35. Woodley J M, Bisschops M, Straathof A J J, et al. Future directions for in-situ product removal (ISPR) [J]. Journal of Chemical Technology and Biotechnology, 2008, 83(2):121-123.
36. Houng J Y, Liau J S. Applying slow-release biocatalysis to the asymmetric reduction of ethyl 4-chloroacetoacetate [J]. Biotechnology Letters, 2003, 25:17-21.
37. Yang Z H, Zeng R, Chang X, et al. Toxicity of aromatic ketone to yeast cell and improvement of the asymmetric reduction of aromatic ketone catalyzed by yeast cell with the introduction of resin adsorption [J]. Food Technology and Biotechnology, 2008, 46(3):322-327.
38. Hilker I, Gutierrez M C, Furstoss R, et al. Preparative scale Baeyer-Villiger biooxidation at high concentration using recombinant Escherichia coli and in situ substrate feeding and product removal process [J]. Nature Protocols, 2008, 3(3):546-554.
39. Vicenzi J T, Zmijewski M J, Reinhard M R, et al. Large-scale stereoselective enzymatic ketone reduction with in situ product removal via polymeric adsorbent resins [J]. Enzyme and Microbial Technology, 1997, 20(7):494-499.
40. D'Arrigo P, Fantoni G P, Servi S, et al. The effect of absorbing resins On substrate concentration and enantiomeric excess in yeast reduction [J]. Tetrahedron: Asymmetry, 1997, 8(14):2375-2379.
41. Coppola G M, Schuster H F. Mandelic acid. In: Walter G, editor.α-Hydroxy acids in enantioselective syntheses. Weinheim: Wiley-VCH 2003. p. 137-165.
42.黄斌,孙兴邦.盐酸奥昔布宁的合成[J].中国医药工业杂志, 1996, 27(9):387-389.
43. Furlenmeier A, Quitt P, Vogler K, et al., inventors; 6-Acyl derivatives of aminopenicillanic acid U.S. patent 3,957,758. 1976.
44. Bichel H, Kocsis K, Peter H, inventors; Cephalosporins having anα-acyloxyacetic acid side chain. U.S. patent 4,067,979. 1978.
45. Mills J, Schmiegel K K, Shaw W N, inventors; Phenethanolamines, compositions containing the same, and method for effecting weight control. U.S. patent 4,391,826. 1983.
46. Surivet J P, Vatele J M. Total synthesis of antitumor Goniothalamus styryllactones [J]. Tetrahedron, 1999, 55(45):13011-13028.
47. Ema T, Okita N, Ide S, et al. Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E-coli: toward practical and green access to clopidogrel [J]. Organic & Biomolecular Chemistry, 2007, 5(8):1175-1176.
48.张金波,杨吉春,刘若霖,等.扁桃酸类杀菌剂的创制及其研究进展[J].农药, 2009, 48(2):82-87.
49. Whitesell J K, Reynolds D. Resolution of chiral alcohols with mandelic acid [J]. Journal of Organic Chemistry, 1983, 48(20):3548-3551.
50. Kinbara K, Sakai K, Hashimoto Y, et al. Design of resolving reagents: p-Substituted mandelic acids as resolving reagents for 1-arylalkylamines [J]. Tetrahedron: Asymmetry, 1996, 7(6):1539-1542.
51. Bauer T, Gaiewiak J. alpha-Hydroxy carboxylic acids as ligands for enantioselective addition reactions of organoaluminum reagents to aromatic and aliphatic aldehydes [J]. Tetrahedron: Asymmetry, 2005, 16(4):851-855.
52. Bauer T, Gajewiak J. alpha-Hydroxy carboxylic acids as ligands for enantioselective diethylzinc additions to aromatic and aliphatic aldehydes [J]. Tetrahedron, 2004, 60(41):9163-9170.
53. Yamazaki Y, Maeda H. Enzymatic synthesis of optically pure (R)-(-)-mandelic acid and other 2- hydroxycarboxylic acids: Screening for the enzyme, and its purification, characterization and use. [J]. Agricultural and Biological Chemistry, 1986, 50(10):2621-2631.
54. Hosono K, Kajiwara S, Yamazaki Y, et al. Construction of a bioreactor for production of (R)-(-)-mandelate, a typical specialty chemical [J]. Journal of Biotechnology, 1990, 14(2):149-156.
55. Vasicracki D, Jonas M, Wandrey C, et al. Continuous (R)-mandelic acid production in an enzyme membrane reactor [J]. Applied Microbiology and Biotechnology, 1989, 31(3):215-222.
56. Xiao M T, Huang Y Y, Shi X A, et al. Bioreduction of phenylglyoxylic acid to R-(-)-mandelic acid by Saccharomyces cerevisiae FD11b [J]. Enzyme and Microbial Technology, 2005, 37(6):589-596.
57.黄雅燕,肖美添,郭养浩.微生物转化苯乙酮酸合成R-(-)-扁桃酸[J].福州大学学报(自然科学版), 2006, 34(3):435-438.
58. Wada Y, Iwai S, Tamura Y, et al. A new family of D-2-hydroxyacid dehydrogenases that comprises D-mandelate dehydrogenases and 2-ketopantoate reductases [J]. Bioscience Biotechnology and Biochemistry, 2008, 72(4):1087-1094.
59. Hummel W, Schutte H, Kula M R. D-(-)-mandelic acid dehydrogenase from Lactobacillus curvatus [J]. Applied Microbiology and Biotechnology, 1988, 28(4-5):433-439.
60. Baker D P, Fewson C A. Purification and characterization of D-(-)-mandelate dehydrogenase from Rhodotorula graminis [J]. Journal of General Microbiology, 1989, 135:2035-2044.
61. Tamura Y, Ohkubo A, Iwai S, et al. Two forms of NAD-dependent D-mandelate dehydrogenase in Enterococcus faecalis IAM 10071 [J]. Applied and Environmental Microbiology, 2002, 68(2):947-951.
62.严芬,郭养浩,陈芬玲,等.酿酒酵母中D-(-)-扁桃酸脱氢酶性质研究[J].福州大学学报(自然科学版), 2008, 36(6):905-909.
63. Milagre H M S, Milagre C D F, Moran P J S, et al. Reduction of ethyl benzoylformate mediated by Saccharomyces cerevisiae entrapped in alginate fibers with double gel layers in a continuously operated reactor [J]. Enzyme and Microbial Technology, 2005, 37(1):121-125.
64. Kratzer R, Egger S, Nidetzky B. Integration of enzyme, strain and reaction engineering to overcome limitations of Baker's yeast in the asymmetric reduction of alpha-keto esters [J]. Biotechnology and Bioengineering, 2008, 101(5):1094-1101.
65. He C M, Chang D L, Zhang J. Asymmetric reduction of substituted alpha- and beta-ketoesters by Bacillus pumilus Phe-C3 [J]. Tetrahedron: Asymmetry, 2008, 19(11):1347-1351.
66. Kayser M M, Mihovilovic M D, Kearns J, et al. Baker's yeast-mediated reductions of alpha-keto esters and an alpha-keto-beta-lactam. Two routes to the paclitaxel side chain [J]. Journal of Organic Chemistry, 1999, 64(18):6603-6608.
67. Chen Y Z, Xu J G, Xu X Y, et al. Enantiocomplementary preparation of (S)- and (R)-mandelic acid derivatives via alpha-hydroxylation of 2-arylacetic acid derivatives and reduction of alpha-ketoester using microbial whole cells [J]. Tetrahedron: Asymmetry, 2007, 18(21):2537-2540.
68. Meyer D, Buehler B, Schmid A. Process and catalyst design objectives for specific redox biocatalysis. Advances in Applied Microbiology, Vol 59. San Diego: Elsevier Academic Press Inc; 2006. p. 53-91.
69. Li G Y, Huang K L, Jiang Y R, et al. Production of (R)-mandelic acid by immobilized cells of Saccharomyces cerevisiae on chitosan carrier [J]. Process Biochemistry, 2007, 42(10):1465-1469.
70. Xiao M T, Huang Y Y, Ye J, et al. Study on the kinetic characteristics of the asymmetric production of R-(-)-mandelic acid with immobilized Saccharomyces cerevisiae FD11b [J]. Biochemical Engineering Journal, 2008, 39(2):311-318.
71. Polizzi K M, Bommarius A S, Broering J M, et al. Stability of biocatalysts [J]. Current Opinion in Microbiology, 2007, 11(2):220-225.
72. Tishkov V I, Popov V O. Protein engineering of formate dehydrogenase [J]. Biomolecular Engineering, 2006, 23(2-3):89-110.
73. Wu J C, He Z M, Yao C Y, et al. Increased activity and stability of Candida rugosa lipase in reverse micelles formed by chemically modified AOT in isooctane [J]. Journal of Chemical Technology and Biotechnology, 2001, 76(9):949-953.
74. Fujita K, Forsyth M, MacFarlane D R, et al. Unexpected improvement in stability and utility of cytochrome c by solution in biocompatible ionic liquids [J]. Biotechnology and Bioengineering, 2006, 94(6):1209-1213.
75. Chen R R Z. Permeability issues in whole-cell bioprocesses and cellular membrane engineering [J]. Applied Microbiology and Biotechnology, 2007, 74(4):730-738.
76.于明安,朱晓冰,祁巍,等. CTAB透性化酵母细胞生物催化合成(S)-(+)-3-羟基丁酸乙酯[J].催化学报, 2005, 26(7):609-613.
77. Zhang J, Witholt B, Li Z. Coupling of permeabilized microorganisms for efficient enantioselective reduction of ketone with cofactor recycling [J]. Chemical Communications, 2006, (4):398-400.
78. Ni Y, Chen R R. Accelerating whole-cell biocatalysis by reducing outer membrane permeability barrier [J]. Biotechnology and Bioengineering, 2004, 87(6):804-811.
79. Zhang B B, Lou W Y, Zong M H, et al. Efficient synthesis of enantiopure (S)-4-(trimethylsilyl)-3-butyn-2-ol via asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one with immobilized Candida parapsilosis CCTCC M203011 cells [J]. Journal of Molecular Catalysis B-Enzymatic, 2008, 54(3-4):122-129.
80. Wang W, Zong M H, Lou W Y. Use of an ionic liquid to improve asymmetric reduction of 4 '-methoxyacetophenone catalyzed by immobilized Rhodotorula sp AS2.2241 cells [J]. Journal of Molecular Catalysis B-Enzymatic, 2009, 56(1):70-76.
81. Stark D, von Stockar U. In situ product removal (ISPR) in whole cell biotechnology during the last twenty years. In: von Stockar U, van der Wielen LAM, editors. Process integration in biochemical engineering: Springer-Verlag New York Inc.; Springer-Verlag GmbH & Co. KG; 2003. p. 149-175.
82. Coward-Kelly G, Chen R R. A Window into Biocatalysis and Biotransformations [J]. Biotechnology Progress, 2007.
83. Woodley J M. New opportunities for biocatalysis: making pharmaceutical processes greener [J]. Trends in Biotechnology, 2008, 26(6):321-327.
84. Straathof A J J, Panke S, Schmid A. The production of fine chemicals by biotransformations [J]. Current Opinion in Biotechnology, 2002, 13(6):548-556.
85. Ishige T, Honda K, Shimizu S. Whole organism biocatalysis [J]. Current Opinion in Chemical Biology, 2005, 9(2):174-180.
86. Schmid A, Dordick J S, Hauer B, et al. Industrial biocatalysis today and tomorrow [J]. Nature, 2001, 409(6817):258-268.
87.张辉.微生物全细胞转化法制备(R)-扁桃酸的研究[D]: [硕士学位论文].无锡:江南大学, 2006.
88.黄汉荣.扁桃酸氧化还原酶的筛选及应用研究[D]: [硕士学位论文].上海:华东理工大学, 2005.
89. Kesslin G, Kelly K W, inventors; Resolution of racemic mandelic acid. U.S. patent 4,322,548. 1982.
90. Schoemaker H E, Mink D, Wubbolts M G. Dispelling the myths - Biocatalysis in industrial synthesis [J]. Science, 2003, 299(5613):1694-1697.
91. Groger H. Enzymatic routes to enantiomerically pure aromatic alpha-hydroxy carboxylic acids: A further example for the diversity of biocatalysis [J]. Advanced Synthesis & Catalysis, 2001, 343(6-7):547-558.
92. Weinstock L M, Currie R B, Lovell A V. A general, one-step synthesis of alpha-keto ester [J]. Synthetic Communications, 1981, 11(12):943-946.
93. Yu M A, Hou Y, Gong G H, et al. Effects of industrial storage on the bioreduction capacity of brewer's yeast [J]. Journal of Industrial Microbiology & Biotechnology, 2009, 36(1):157-162.
94. Kaluzna I A, Rozzell J D, Kambourakis S. Ketoreductases: stereoselective catalysts for the facile synthesis of chiral alcohols [J]. Tetrahedron: Asymmetry, 2005, 16(22):3682-3689.
95. Zhu D M, Stearns J E, Ramirez M, et al. Enzymatic enantioselective reduction of alpha-ketoesters by a thermostable 7 alpha-hydroxysteroid dehydrogenase from Bacteroides fragilis [J]. Tetrahedron, 2006, 62(18):4535-4539.
96. Zhu D M, Yang Y, Buynak J D, et al. Stereoselective ketone reduction by a carbonyl reductase from Sporobolomyces salmonicolor. Substrate specificity, enantioselectivity and enzyme-substrate docking studies [J]. Organic & Biomolecular Chemistry, 2006, 4(14):2690-2695.
97. Wei Z L, Li Z Y, Lin G Q. anti-Prelog microbial reduction of aryl alpha-halomethyl or alpha-hydroxymethyl ketones with Geotrichum sp 38 [J]. Tetrahedron, 1998, 54(43):13059-13072.
98. Fronza G, Fuganti C, Grasselli P, et al. On the mode of bakers-yeast transformation of 3-chloropropiophenone and related ketones - synthesis of (2S)-[2,2H]propiophenone, (R)-fluoxetine, (R)-fenfluramine and (S)-fenfluramine [J]. Journal of Organic Chemistry, 1991, 56(21):6019-6023.
99. Kumar A, Ner D H, Dike S Y. A new chemoenzymatic enantioselective synthesis of R-(-)-tomoxetine, (R)-fluoxetine and (S)-fluoxetine [J]. Tetrahedron Letters, 1991, 32(16):1901-1904.
100. Yamazaki N, Atobe M, Kibayashi C. Nucleophilic addition of methyllithium to chiral oxime ethers: asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue [J]. Tetrahedron Letters, 2001, 42(30):5029-5032.
101. Kumar P, Upadhyay R K, Pandey R K. Asymmetric dihydroxylation route to (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine [J]. Tetrahedron-Asymmetry, 2004, 15(24):3955-3959.
102.何军邀.微生物细胞非水相催化羰基化合物的不对称还原[D]: [博士学位论文].无锡:江南大学, 2006.
103.徐小琳,徐岩,穆晓清. NAD(P)依赖型氧化还原酶分离纯化技术进展[J].工业微生物, 2005, 35(1):49-54.
104.汪家政,范明.蛋白质技术手册:科学出版社; 2000.
105. Bradford M M. Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding [J]. Analytical Biochemistry, 1976, 72(1-2):248-254.
106. Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacterio phage T-4 [J]. Nature (London), 1970, 227(5259):680-685.
107.Zheng Y C, Si X H, He Q H, et al. Yak lactate dehydrogenase A4: Purification, properties, and cDNA cloning [J]. Bioscience Biotechnology and Biochemistry, 2008, 72(9):2448-2451.
108. Eprintsev A T, Klimova M A, Shikhalieva K D, et al. Isolation and purification of malate dehydrogenase isoforms from phototrophic purple bacteria Rhodobacter sphaeroides and Rhodopseudomonas palustris [J]. Biology Bulletin, 2008, 35(6):585-591.
109.严芬,郭养浩,林木仙,等.酿酒酵母中的D-(-)-扁桃酸脱氢酶[J].药物生物技术, 2007, 14(1):43-47.
110. Engelking H, Pfaller R, Wich G, et al. Reaction engineering studies on beta-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae [J]. Enzyme and Microbial Technology, 2006, 38(3-4):536-544.
111. He J Y, Zhou L M, Wang P, et al. Microbial reduction of ethyl acetoacetate to ethyl (R)-3-hydroxybutyrate in an ionic liquid containing system [J]. Process Biochemistry, 2009, 44(3):316-321.
112. Slavik J, Kotyk A. Intracellular pH distribution and transmembrane pH profile of yeast-cells [J]. Biochimica Et Biophysica Acta, 1984, 766(3):679-684.
113. Phillips R S. Temperature modulation of the stereochemistry of enzymatic catalysis: Prospects for exploitation [J]. Trends in Biotechnology, 1996, 14(1):13-16.
114. Sih C J, Chen C S. Microbial asymmetric catalysis - enantioselective reduction of ketones [J]. Angewandte Chemie-International Edition in English, 1984, 23(8):570-578.
115. Woodley J M. Microbial biocatalytic processes and their development. Advances in Applied Microbiology, Vol 60. San Diego: Elsevier Academic Press Inc; 2006. p. 1-15.
116. Hu X P, Mamoto R, Shimomura Y, et al. Cell surface structure enhancing uptake of polyvinyl alcohol (PVA) is induced by PVA in the PVA-utilizing Sphingopyxis sp strain 113P3 [J]. Archives of Microbiology, 2007, 188(3):235-241.
117. Guo J L, Mu X Q, Zheng C G, et al. A highly stable whole-cell biocatalyst for the enantioselective synthesis of optically active alpha-hydroxy acids [J]. Journal of Chemical Technology and Biotechnology, 2009, 84(12):1787-1792.
118. Pscheidt B, Glieder A. Yeast cell factories for fine chemical and API production [J]. Microbial Cell Factories, 2008, 7:49.
119. Secundo F, Phillips R S. Effects of pH on enantiospecificity of alcohol dehydrogenases from Thermoanaerobacter ethanolicus and horse liver [J]. Enzyme and Microbial Technology, 1996, 19(7):487-492.
120. Phillips R S. Temperature effects on stereochemistry of enzymatic reactions [J]. Enzyme and Microbial Technology, 1992, 14(5):417-419.
121. Leon R, Fernandes P, Pinheiro H M, et al. Whole-cell biocatalysis in organic media [J]. Enzyme and Microbial Technology, 1998, 23(7-8):483-500.
122. Zhang B L, Pionnier S. Cofactor recycling mechanism in asymmetric biocatalytic reduction of carbonyl compounds mediated by yeast: Which is the efficient electron donor? [J]. Chemistry-a European Journal, 2003, 9(15):3604-3610.
123.高炳学,林金萍,魏东芝.酿酒酵母不对称合成(R)-(-)-扁桃酸甲酯[J].华东理工大学学报(自然科学版), 2008, 34(3):350-353.
124. Bechtold M, Panke S. In situ Product Recovery Integrated with Biotransformations [J]. Chimia, 2009, 63(6):345-348.
125. Kim P Y, Pollard D J, Woodley J M. Substrate supply for effective biocatalysis [J]. Biotechnology Progress, 2007, 23(1):74-82.
126. Han K, Levenspiel O. Extended monod kinetics for substrate, product, and cell-inhibition [J]. Biotechnology and Bioengineering, 1988, 32(4):430-437.
127. Amanullah A, Hewitt C J, Nienow A W, et al. Fed-batch bioconversion of indene to cis-indandiol [J]. Enzyme and Microbial Technology, 2002, 31(7):954-967.
128. Chin-Joe I, Straathof A J J, Pronk J T, et al. Effect of high product concentration in a dual fed-batch asymmetric 3-oxo ester reduction by baker's yeast [J]. Biocatalysis and Biotransformation, 2002, 20(5):337-345.
129. Casey J T, Walsh P K, O’Shea D G. Characterisation of adsorbent resins for the recovery of geldanamycin from fermentation broth [J]. Separation and Purification Technology, 2006.
130. Dongliang H, Cuiqing M, Lifu S, et al. Enhanced vanillin production from ferulic acid using adsorbent resin [J]. Applied Microbiology and Biotechnology, 2007, 74(4):783-790.
131. Roddick F A, Britz M L. Production of hexanoic acid by free and immobilised cells of Megasphaera elsdenii: Influence of in-situ product removal using ion exchange resin [J]. Journal of Chemical Technology and Biotechnology, 1997, 69(3):383-391.
132. van den Berg C, Wierckx N, Vente J, et al. Solvent-impregnated resins as an in situ product recovery tool for phenol recovery from Pseudomonas putida S12TPL fermentations [J]. Biotechnology and Bioengineering, 2008, 100(3):466-472.
133. Hilker I, Gutierrez M C, Alphand V, et al. Microbioloical transformations 57. Facile and efficient resin-based in situ SFPR preparative-scale synthesis of an enantiopure "unexpected" lactone regioisomer via a Baeyer-Villiger oxidation process [J]. Organic Letters, 2004, 6(12):1955-1958.
134. Ni Y, Xu Y, Yang W, et al. Promoting effect of resin adsorption on asymmetric reduction of acetophenone catalyzed by Rhodotorula sp Cells [J]. Chinese Journal of Organic Chemistry, 2008, 28(12):2137-2141.
135. Hilker I, Wohlgemuth R, Alphand V, et al. Scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity using a resin-based in situ SFPR strategy [J]. Biotechnology and Bioengineering, 2005, 92(6):702-710.
136. Hilker I, Alphand V, Wohlgemuth R, et al. Microbial transformations, 56. Preparative scale asymmetric Baeyer-Villiger oxidation using a highly productive "two-in-One" resin-based in situ SFPR concept [J]. Advanced Synthesis & Catalysis, 2004, 346(2-3):203-214.
137. Darrigo P, Fantoni G P, Servi S, et al. The effect of absorbing resins on substrate concentration and enantiomeric excess in yeast reduction [J]. Tetrahedron: Asymmetry, 1997, 8(14):2375-2379.